Project abstract The goal of this project is to understand the role Nrf1 in cellular stress response pathway. We hypothesize that depending on the type of stimuli, different Nrf1 isoforms regulate different adaptive responses (oxidative, ER, proteotoxic) to cellular stress. We will first determine stress-activated genes that are controlled by Nrf1 and its isoforms. Next, we will use genome-wide approaches that will permit comprehensive, and quantitative analyses to investigate redundancy and specificity between Nrf1 and Nrf2 in mediating cellular stress responses. Third, we will delineate mechanisms by which Nrf1 is regulated. Our findings should have broad and significant impact on our understanding of cellular stress response pathways.